Increase in the constrictor effects of Rho-kinase in skeletal muscle and coronary arteries of rats with chronic hypothyroidism

Abstract

Aim. The deficit of thyroid function is known to be accompanied by an increase in the overall peripheral vascular resistance. This work tested the hypothesis that long-term hypothyroidism leads to an increase in the vasoconstrictor effect of Rho-kinase in skeletal muscle and heart resistance arteries of adult rats.Materials and methods.Male Wistar rats consumed the antithyroid drug propylthiouracil (PTU) in drinking water (0.025%), starting at 10 weeks of age. The rats of the control group received PTU-free water. After 14 weeks, the contractile responses of the gastrocnemius muscle arteries (to the α1-adrenoceptor agonist methoxamine) and the septal coronary artery (to the thromboxane A2 receptor agonist U46619) were isometrically recorded. The contribution of the Rho-kinase to the arterial contractile responses was assessed using inhibitor Y27632 (3 μM).Results.The consumption of propylthiouracil was accompanied by a marked decrease of thyroid hormone concentrations and an increase in total cholesterol serum level as well as a decrease in body weight. Maximal contractile responses of studied arteries were also reduced in hypothyroid rats. However, basal tone and reactivity to the moderate concentrations of agonists in arteries of hypothyroid rats were increased compared to control animals. Y27632 significantly weakened the contractile responses of the arteries and negated the differences between the two groups of rats.Conclusion.Chronic hypothyroidism leads to an increase in the activity of the Rho-kinase signaling pathway in the arteries of the gastrocnemius muscle and heart, which results in the increase of the spontaneous tone of the arteries and their reactivity to agonists.